Archives of Gynecology and Obstetrics (2021) 304:5–38

https://doi.org/10.1007/s00404-021-06049-z

REVIEW

A systematic review of pregnant women with COVID‑19 and their

neonates
Mona Mirbeyk1,2 · Amene Saghazadeh1,2 · Nima Rezaei2,3,4,5

Received: 11 July 2020 / Accepted: 27 March 2021 / Published online: 2 April 2021
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021

Abstract
Background In December 2019, a novel coronavirus disease (COVID-19) emerged in Wuhan, China, with an incredible
contagion rate. However, the vertical transmission of COVID-19 is uncertain.
Objectives This is a systematic review of published studies concerning pregnant women with confirmed COVID-19 and
their neonates.
Search strategy We carried out a systematic search in multiple databases, including PubMed, Web of Science, Google
Scholar, Scopus, and WHO COVID-19 database using the following keywords: (Coronavirus) OR (novel coronavirus) OR
(COVID-19) OR (COVID19) OR (COVID 19) OR (SARS-CoV2) OR (2019-nCoV)) and ((pregnancy) OR (pregnant) OR
(vertical transmission) OR (neonate) OR (newborn) OR (placenta) OR (fetus) OR (Fetal)). The search took place in April
2020.
Selection criteria Original articles published in English were eligible if they included pregnant patients infected with COVID-
19 and their newborns.
Data collection and analyses The outcomes of interest consisted of clinical manifestations of COVID-19 in pregnant patients
with COVID-19 and also the effect of COVID-19 on neonatal and pregnancy outcomes.
Main results 37 articles involving 364 pregnant women with COVID-19 and 302 neonates were included. The vast majority
of pregnant patients were in their third trimester of pregnancy, and only 45 cases were in the first or second trimester (12.4%).
Most mothers described mild to moderate manifestations of COVID-19. Of 364 pregnant women, 25 were asymptomatic at
the time of admission. The most common symptoms were fever (62.4%) and cough (45.3%). Two maternal deaths occurred.
Some pregnant patients (12.1%) had a negative SARS‐CoV‐2 test but displayed clinical manifestations and abnormalities in
computed tomography (CT) scan related to COVID‐19. Twenty‐two (6.0%) pregnant patients developed severe pneumonia.
Two maternal deaths occurred from severe pneumonia and multiple organ dysfunction. Studies included a total of 302 neo-
nates from mothers with COVID‐19. Of the studies that provided data on the timing of birth, there were 65 (23.6%) preterm
neonates. One baby was born dead from a mother who also died from COVID-19. Of the babies born alive from mothers with
COVID‐19, five newborns faced critical conditions, and two later died. A total of 219 neonates underwent nasopharyngeal
specimen collection for SARS‐CoV‐2, of which 11 tested positive (5%). Seventeen studies examined samples of the placenta,
breast milk, umbilical cord, and amniotic fluid, and all tested negative except one amniotic fluid sample.
Conclusions A systematic review of published studies confirm that the course of COVID-19 in pregnant women resembles
that of other populations. However, there is not sufficient evidence to establish an idea that COVID-19 would not complicate
pregnancy.

Keywords COVID-19 · Immunity · Neonates · Pregnancy · SARS-CoV2 · Vertical transmission

3
* Nima Rezaei Department of Immunology, School of Medicine, Tehran
[email protected]; [email protected] University of Medical Sciences, Tehran, Iran
4
1 Network of Immunity in Infection, Malignancy
Systematic Review and Meta‑Analysis Expert Group
and Autoimmunity (NIIMA), Universal Scientific Education
(SRMEG), Universal Scientific Education and Research
and Research Network (USERN), Tehran, Iran
Network (USERN), Tehran, Iran
5
2 Children’s Medical Center Hospital, Dr. Qarib St, Keshavarz
Research Center for Immunodeficiencies, Children’s Medical
Blvd, 14194 Tehran, Iran
Center, Tehran University of Medical Sciences, Tehran, Iran

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6 Archives of Gynecology and Obstetrics (2021) 304:5–38

Background Scopus, and WHO COVID-19 database using the follow-

ing keywords: (Coronavirus) OR (novel coronavirus) OR
The World Health Organization (WHO) announced the (COVID-19) OR (COVID19) OR (COVID 19) OR (SARS-
novel coronavirus disease (COVID-19) as a Pandemic on CoV2) OR (2019-nCoV)) and ((pregnancy) OR (pregnant)
March 7, 2020, when the number of confirmed cases just OR (vertical transmission) OR (neonate) OR (newborn) OR
exceeded 100,000 [1]. As of April 21, 2020, COVID-19 has (placenta) OR (fetus) OR (Fetal)). The search took place in
reached all over the world, with about 180,000 deaths of a April 2020 (Fig. 1).
total of more than 2 million confirmed cases. Moreover, it
seems there is an underestimation in the mortality rate of Selection criteria
this infectious disease. Studies estimate the real mortality
rate to be about 6% in China, rising to about 15% in other We sought studies that investigated the potential effect of
countries [2]. Therefore, COVID-19 is, in general, a life- COVID-19 on pregnancy and neonatal health. Original arti-
threatening condition. cles published in English were eligible if they included preg-
COVID-19 can affect multiple organs and systems nant patients infected with COVID-19 and their newborns.
[3–11], although it mainly involves the respiratory system, The outcomes of interest consisted of clinical manifesta-
where its involvement can cause a wide range of symptoms tions of COVID-19 in pregnant patients with COVID-19
from a common cold to severe respiratory distress [12–15]. and also, the effect of COVID-19 on neonatal and pregnancy
In particular, the disease is more severe and deadly in older outcomes.
age groups and people who have pre-existing comorbidity.
The immunopathogenesis of the disease is not clear [16–21]. Data extraction
However, as for other infectious conditions, immune dys-
regulation might increase the risk of severe illness and death For pregnant women infected with COVID-19, we extracted
from COVID-19 [21–27]. the following data: article title, author, study type, coun-
Pregnancy is a particular condition that can have signifi- try, number of pregnant women with COVID-19, clinical
cant effects on the biological systems of a woman’s body. manifestations of disease in pregnant women, the trimes-
Notably, pregnant women acquire changes so that their ter of pregnancy, diagnostic technique, potential compli-
immune system will be able to tolerate pregnancy. These cations related to COVID-19, delivery, and the maternal
changes mostly place the maternal immune system under outcome(s) of COVID-19. For neonates born from moth-
a down-regulated condition. As a result, pregnant women ers with COVID-19, data on the article title, author, study
are generally considered vulnerable to infectious diseases. type, country, number of neonates, neonatal maturity, clini-
Whereas its transmission mainly occurs through human- cal presentation, neonatal complications, a diagnostic test
to-human contact, the novel coronavirus has shown its for COVID-19, Apgar score, and neonatal outcome were
potential to transmit via multiple transmission routes [28] extracted. Finally, for pregnancy outcomes, we collected
and affect both children and adults [13, 29]. It, however, data on the article title, author, study type, country, placen-
remained unclear whether or not this potentially fatal virus tal test for viral nucleic acid, and pregnancy complications.
can vertically be transmitted and what are the possible
effects of the disease on the pregnancy outcomes.
Results

Literature search
Methods
The systematic search yielded a total of 1068 search
The present systematic review was developed according results, of which 785 discrete records remained for screen-
to the preferred reporting items for systematic reviews and ing after removing duplicates. During title and abstract
meta-analyses (PRISMA) statement [14]. Before the study screening, we selected 48 articles for detailed review. In
begins, the authors developed the study protocol that is the detailed review process, we excluded thirteen articles
available on request. with the following reasons for exclusion: seven articles not
provided data on pregnant patients or neonatal outcomes
[28, 30–35], three studies lacked data on neonates or ver-
Literature search tical transmission [36–38], one study reported a 17-day
neonate who had exposure to parents complaining of fever
We carried out a systematic search in multiple databases, and cough [39], one study was not original research [40],
including PubMed, Web of Science, Google Scholar, and the full-text was not available for one article [41].

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Archives of Gynecology and Obstetrics (2021) 304:5–38 7

Fig. 1  PRISMA flowchart of the literature search

Also, we carried out an additional search through review- Clinical presentation of COVID‑2019 in pregnant
ing reference lists of 35 included articles from systematic women
search and related review articles and found two additional
articles [42, 43]. Finally, a total number of 37 studies, Of 37 studies, two provided no data on clinical symptoms of
including case reports and case series, were eligible to be pregnant patients [43, 44]. A total of 364 pregnant women
included in this systematic review [42–76]. Tables 1, 2, 3 was, thus, included in the data synthesis of clinical manifes-
provide an overview of the characteristics of the included tations of COVID-19 in pregnant women.
studies. Below is a narrative synthesis of studies that Of 364 pregnant women, 25 were asymptomatic at the
included pregnant women with confirmed COVID-19 and time of admission. The most common symptoms were fever
their neonates. (62.4%) and cough (45.3%). The other common symptoms

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Table 1  Characteristics of pregnant women with COVID-19 included in the systematic review
Article title Author Study type Country Number of Clinical The onset of Diagnosing Complications Delivery The maternal
patients features of the disease presen- technique due to viral outcome(s) of

13
disease in preg- tation infection disease in preg-
nant patients (= N) nant patients

Preg- Chen et al. Case study China 3 Fever (= 3) Third trimester 2 cases: posi- None Cesarean sec- 2 patients
nant women (= 3) tive nucleic tion (= 3) cured and
with acid test discharged;
new coronavi- through throat one underwent
rus infection: swab, isolation treat-
a clinical 1 case: clinical ment
characteristics confirmation
and placental
pathological
analysis of
three cases
Clinical analy- Zhu et al. Case study China 9 Fever (= 7) Third trimes- Chest CT scan None Cesarean sec- Cured and
sis of 10 neo- Cough (= 4) ter* and throat tion (= 7) discharged
nates born to Cholecystitis swab nucleic Vaginal deliv-
mothers with (= 1) acid testing** ery (= 2)
2019-nCoV Diarrhea (= 1)
pneumonia
Clinical charac- Chen et al. Case study China 9 Fever (= 7) Third trimester CT scan of None Cesarean sec- Cured and
teristics and Cough (= 4) lung and tion (= 9) discharged
intrauterine Myalgia (= 3) throat swab
vertical Sore throat nucleic acid
transmission (= 2) testing
potential Malaise (= 2)
of COVID-
19 infection
in nine preg-
nant women:
a retrospec-
tive review
of medical
records
Analysis of Zhang et al. Case–control China 16 15 moderate Third trimester Clinical Severe case Cesarean sec- Cured and
the preg- (45 case and 1 diagnosis and (= 1) tion (= 16) discharged
nancy out- Controls) severe case of throat swab
comes pneumonia nucleic acid
in preg- detection
nant women
with COVID-
19 in Hubei
Province
Archives of Gynecology and Obstetrics (2021) 304:5–38
 Table 1  (continued)
Article title Author Study type Country Number of Clinical The onset of Diagnosing Complications Delivery The maternal
patients features of the disease presen- technique due to viral outcome(s) of
disease in preg- tation infection disease in preg-
nant patients (= N) nant patients

Clinical mani- Liu et al. Case Study China 13 Fever (= 10) Third trimester Clinical symp- Severe pneu- Cesarean sec- Cured and
festations and Dyspnea (= 3) (= 11), toms and monia and tion (= 10) discharged
outcome of Fatigue (= 2) Less than throat swab intubation Still pregnant One case still in
SARS-CoV-2 Cough (= 2) 28 weeks GA nucleic acid (= 1) (= 3) the hospital
infection dur- Sore throat (= 2) detection
ing pregnancy (= 1)
No symptoms
(= 1)
Lack of vertical Li et al. Case Report China 1 Cough and Third trimester Clinical symp- None Cesarean sec- Cured and
transmission temperature toms and tion discharged
of severe of 37.2 °C throat swab
Archives of Gynecology and Obstetrics (2021) 304:5–38

acute nucleic acid

respiratory detection
syndrome
Coronavirus
2, China
A case of Wang et al. Case Report China 1 Fever Third trimester Clinical None Cesarean sec- Cured and
2019 Novel symptoms tion discharged
Coronavirus and Chest
in a pregnant CT scan and
woman with throat swab
preterm nucleic acid
delivery detection
A case report Wang et al. Case report China 1 Fever Third trimester Clinical None Cesarean sec- Cured and
of neonatal symptoms tion discharged
COVID-19 and Chest
infection in CT scan and
China throat swab
nucleic acid
detection
Perinatal Fan et al. Case report China 2 Fever (= 2) Third trimester Clinical None Cesarean sec- One case still in
transmission Nasal conges- symptoms tion (= 2) the hospital
of COVID-19 tion (= 2) and Chest One case cured
associated Chill (= 1) CT scan and and discharged
SARS-CoV-2: Sore throat throat swab
should we (= 1) nucleic acid
worry? Abdominal detection
rush (= 1)

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Table 1  (continued)
Article title Author Study type Country Number of Clinical The onset of Diagnosing Complications Delivery The maternal
patients features of the disease presen- technique due to viral outcome(s) of

13
disease in preg- tation infection disease in preg-
nant patients (= N) nant patients

Clinical Chen et al. Case series China 5 Fever (= 5) Third trimester Clinical None Cesarean sec- No death was
analysis of Coryza (= 1) (= 5) symptoms tion (= 2) reported
pregnant Sputum (= 1) and Chest Vaginal deliv-
women with Cough (= 1) CT scan and ery (= 3)
2019 Novel SARS-CoV-2
Coronavirus quantitative
Pneumonia RT-PCR
Possible Dong et al. Case report China 1 Fever and Nasal Third trimester Clinical None Cesarean sec- Cured and
vertical congestion symptoms tion discharged
transmission and Chest
of SARS- CT scan and
CoV-2 From throat swab
an infected nucleic acid
mother to her detection
newborn
Lung ultra- Kalafat et al. Case report Turkey 1 Cough and Third trimester Clinical Severe pneu- Cesarean sec- Still in hospital
sound and shortness of symptoms monia and tion
computed breath and Chest intubation
tomographic CT scan and
findings in throat swab
a pregnant nucleic acid
woman with detection
COVID-19
Coronavirus Liu et al. Case series China 3 Fever (= 2) Third trimester Clinical None Cesarean sec- No death was
disease 2019 Cough (= 1) (= 3) symptoms tion (= 2) reported
(COVID-19) and Chest Vaginal deliv-
during preg- CT scan and ery (= 1)
nancy: a case throat swab
series nucleic acid
detection
Maternal and Li et al. Case–control China 16 Fever (= 12) Third trimester Clinical None Cesarean sec- No death was
neonatal (= 16) symptoms tion (= 14) reported
outcomes and Chest Vaginal deliv- Cured and dis-
of pregnant CT scan and ery (= 2) charged (= 8)
women with throat swab
COVID-19 nucleic acid
pneumonia: a detection
case–control
study
Archives of Gynecology and Obstetrics (2021) 304:5–38
 Table 1  (continued)
Article title Author Study type Country Number of Clinical The onset of Diagnosing Complications Delivery The maternal
patients features of the disease presen- technique due to viral outcome(s) of
disease in preg- tation infection disease in preg-
nant patients (= N) nant patients

A pregnant Zambrano et al. Case report The United 1 Fever, Third trimester Clinical symp- None Vaginal deliv- No death was
woman with States, headache, toms and ery reported
COVID-19 USA myalgia, and throat swab
in Central cough nucleic acid
America detection
Pregnancy and Liu et al. Cross-sectional China 15 Fever (= 13) Third trimester Clinical None Cesarean sec- All patients
perinatal Cough (= 9) (= 13) symptoms tion (= 10) survived
outcomes of Fatigue (= 4) Second trimes- and Chest Vaginal deliv-
women with Muscle ache ter (= 2) CT scan and ery (= 1)
coronavi- (= 3) throat swab Still pregnant
rus disease Dyspnea (= 1) nucleic acid (= 4)
Archives of Gynecology and Obstetrics (2021) 304:5–38

(COVID-19) Sore throat detection

pneumonia: (= 1)
a preliminary Diarrhea (= 1)
analysis No clinical
symptoms
(= 1)
Post-partum
fever (= 1)
Clinical Yu et al. Retrospective China 7 Fever (= 6) Third trimester Clinical None Cesarean sec- Cured and dis-
features and study Cough (= 1) (= 7) symptoms tion charged (= 7)
obstetric Dyspnea (= 1) and Chest (= 7)
and neonatal Diarrhea (= 1) CT scan and
outcomes throat swab
of pregnant nucleic acid
patients with detection
COVID-19
in Wuhan,
China: a
retrospective,
single-center,
descriptive
study

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Table 1  (continued)
Article title Author Study type Country Number of Clinical The onset of Diagnosing Complications Delivery The maternal
patients features of the disease presen- technique due to viral outcome(s) of

13
disease in preg- tation infection disease in preg-
nant patients (= N) nant patients

Neonatal Zeng et al. Cohort study China 33 Fever on Third trimester Clinical None Cesarean sec- No death was
early-onset admission symptoms tion reported
Infection with (= 8) and Chest (= 26)
SARS CoV-2 Cough (= 10) CT scan and Vaginal deliv-
in 33 neo- Post-partum throat swab ery (7)
nates born to fever (= 5) nucleic acid
mothers With detection
COVID-19
in Wuhan,
China
Mortality of Karami et al. Case report Iran 1 Fever Third trimester Clinical Multiple organ Vaginal deliv- Not survived
a pregnant Myalgia symptoms dysfunction ery
patient diag- Cough and Chest and death
nosed with CT scan and
COVID-19: throat swab
a case report nucleic acid
with clinical, detection
radiological,
and histo-
pathological
findings
Unlikely Peng et al. Case report China 1 Fever Third trimester Clinical Not reported Cesarean sec- Survived
SARS-CoV-2 Fatigue symptoms tion
vertical trans- Shortness of and Chest
mission from breath CT scan and
mother to throat swab
child: a case nucleic acid
report detection
Severe COVID- Alzamora et al. Case report The United 1 Fever (low Third trimester Clinical Severe pneu- Cesarean sec- No death was
19 during States, grade) symptoms monia and tion reported
pregnancy USA Shortness of and Chest intubation
and possible breath CT scan and
vertical trans- Malaise throat swab
mission nucleic acid
detection
Archives of Gynecology and Obstetrics (2021) 304:5–38
 Table 1  (continued)
Article title Author Study type Country Number of Clinical The onset of Diagnosing Complications Delivery The maternal
patients features of the disease presen- technique due to viral outcome(s) of
disease in preg- tation infection disease in preg-
nant patients (= N) nant patients

Preterm deliv- Zamanian Case report Iran 1 Fever Third trimester Clinical Severe pneu- Cesarean sec- Not survived
ery in a preg- et al. Myalgia symptoms monia and tion
nant woman Nausea and Chest intubation
with critical Cough CT scan and
COVID-19 Dyspnea throat swab
pneumonia Anorexia nucleic acid
and vertical detection
transmission
Vaginal deliv- Xiong et al. Case report China 1 Fever Third trimester Clinical Not reported Vaginal deliv- Healthy and
ery report of Cough symptoms ery discharged
a healthy neo- Shivering and Chest
Archives of Gynecology and Obstetrics (2021) 304:5–38

nate born to a CT scan and

convalescent throat swab
mother with nucleic acid
COVID-19 detection
Association of Khan et al. Case series China 17 Cough (= 6) Third trimester Clinical Not reported Cesarean sec- No case of death
COVID-19 Fever (= 3) (= 17) symptoms tion (= 17) was reported
infection with Diarrhea (= 3) and Chest CT
pregnancy Nasal conges- scan and/or
outcomes in tion (= 2) throat swab
healthcare shortness of nucleic acid
workers breath (= 2) detection
and general Sputum pro-
women duction (= 1)
Impact of Khan et al. Case report China 3 Fever (= 2) Third trimester Clinical symp- Not reported Vaginal deliv- No case of death
COVID-19 Cough (= 3) (= 3) toms throat ery (= 3) was reported
infection on Chest tightness swab nucleic
pregnancy (= 1) acid detection
outcomes
and the risk
of maternal-
to- neonatal
intrapartum
transmission
of COVID-19
during natural
birth

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Table 1  (continued)
Article title Author Study type Country Number of Clinical The onset of Diagnosing Complications Delivery The maternal
patients features of the disease presen- technique due to viral outcome(s) of

13
disease in preg- tation infection disease in preg-
nant patients (= N) nant patients

Clinical charac- Liu et al. Retrospective China 19 Fever (= 11) Third trimester Clinical diag- Not reported Cesarean sec- No case of death
teristics of 19 study Cough (= 5) (19) nosis (= 9) tion (= 18) was reported
neonates born Diarrhea (= 2) Laboratory Vaginal deliv-
to mothers confirmed ery (= 1)
with COVID- (= 10)
19
COVID-19 Breslin et al. Cohort study The United 43 No symptoms Third trimester Clinical symp- Severe case Cesarean sec- No case of death
infection States, (= 14) (43) toms and (= 4) tion (= 8) was reported
among USA Fever (= 14) throat swab Intubation and Vaginal deliv-
asymptomatic Cough (= 19) nucleic acid ICU admis- ery (= 10)
and sympto- Myalgias or detection sion (= 2) Discharge for
matic preg- fatigue (= 11) continuing
nant women: Dyspnea (= 7) pregnancy
two weeks Chest pain (= 25)
of confirmed (= 5)
presentations Headache (= 8)
to an affiliated
pair of New
York City
hospitals
Clinical Yang et al. Case–control China 13 (42 controls) Prenatal fever Third trimester Clinical Not reported Cesarean sec- No case of death
features and (= 2) symptoms tion (= 9) was reported
outcomes Postpartum and Chest CT Vaginal deliv-
of pregnant Fever (= 8) scan and/or ery (= 4)
women Cough (= 2) throat swab
suspected of nucleic acid
Coronavirus detection
Disease 2019
Asymptomatic Renbin et al. Case report China 1 Asymptomatic Third trimester Chest CT scan Not reported Cesarean sec- No case of death
COVID-19 and throat tion was reported
in pregnant swab nucleic
woman with acid detection
typical chest
CT manifesta-
tion: a case
report
Archives of Gynecology and Obstetrics (2021) 304:5–38
 Table 1  (continued)
Article title Author Study type Country Number of Clinical The onset of Diagnosing Complications Delivery The maternal
patients features of the disease presen- technique due to viral outcome(s) of
disease in preg- tation infection disease in preg-
nant patients (= N) nant patients

Chest CT Liao et al. Case report China 1 Fatigue Third trimester Clinical Not reported Cesarean sec- No case of death
Findings in Cough symptoms tion was reported
a Pregnant and Chest
patient with CT scan and
2019 Novel throat swab
Coronavirus nucleic acid
Disease detection
Infants born Chen et al. Case report China 4 Fever (= 3) Third trimester Clinical Not reported Cesarean sec- No case of death
to mothers Cough (= 2) (= 4) symptoms tion (= 3) was reported
with a new Headache (= 2) and Chest Vaginal deliv-
Coronavirus CT scan and ery (= 1)
Archives of Gynecology and Obstetrics (2021) 304:5–38

(COVID-19) throat swab

nucleic acid
detection
Anesthetic Song et al. Case report China 1 Fever Third trimester Clinical Not reported Cesarean sec- No case of death
management Cough symptoms tion was reported
for emergent Myalgia and Chest
cesarean CT scan and
delivery in throat swab
a parturient nucleic acid
with recent detection
diagnosis of
Coronavirus
Disease 2019
(COVID-19):
a case report
Clinical charac- Yang et al. Case series China 7 Fever (= 5) Third trimester Clinical Not reported Cesarean sec- No case of death
teristics and Cough (= 1) (= 7) symptoms tion (= 7) was reported
risk assess- Diarrhea (= 1) and Chest
ment of new- Abdominal CT scan and
borns born to pain (= 1) throat swab
mothers with nucleic acid
COVID-19 detection
COVID-19 in Breslin et al. Case series The United 7 Fever (= 2) Third trimester Clinical Intubation and Cesarean Sec- No case of death
pregnancy: States, Cough (= 3) (= 7) symptoms ICU admis- tion was reported
early lessons USA Myalgia (= 3) and Chest sion (= 2) (= 2)
Headache (= 2) CT scan and No report
Asymptomatic throat swab of other 5
(= 2) nucleic acid patients
detection

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Table 1  (continued)
Article title Author Study type Country Number of Clinical The onset of Diagnosing Complications Delivery The maternal
patients features of the disease presen- technique due to viral outcome(s) of

13
disease in preg- tation infection disease in preg-
nant patients (= N) nant patients

Antibodies in Zeng et al. Case study China 6 Mild clinical Third trimester Clinical None Cesarean sec- No case of death
infants born presentations (= 6) symptoms tion (= 6) was reported
to mothers (= 6) and Chest
with COVID- CT scan and
19 Pneumonia throat swab
nucleic acid
detection
Novel Zhang et al. Case series China 4 Fever (= 3) Third trimester Clinical None Cesarean sec- No case of death
Coronavirus Cough (= 2) (= 4) symptoms tion (= 4) was reported
infection A decrease in and Chest
in newborn appetite (= 1) CT scan and
babies under Oil intolerance throat swab
28 days in (= 1) nucleic acid
China detection
Clinical char- Chen et al. Retrospective China 118 Fever (= 84) Third trimester 84 women 9 severe case Cesarean sec- No case of death
acteristics study Cough (= 82) (= 75) confirmed and 1 need of tion (= 63) was reported
of pregnant Chest tightness First or second with Nucleic mechanical Vaginal deliv-
women with (= 20) trimester acid testing ventilation ery (= 5)
Covid-19 in Fatigue (= 19) (= 43) and 34 others Spontaneous
Wuhan, China Dyspnea (= 8) diagnosed abortion (= 3)
Diarrhea (= 8) with CT scan Ectopic preg-
Headache (= 7) nancy (= 2)
Asymptomatic Induced abor-
(= 6) tion (= 4)
Still pregnant
(= 41)
Archives of Gynecology and Obstetrics (2021) 304:5–38
 Table 1  (continued)
Article title Author Study type Country Number of Clinical The onset of Diagnosing Complications Delivery The maternal
patients features of the disease presen- technique due to viral outcome(s) of
disease in preg- tation infection disease in preg-
nant patients (= N) nant patients
Summary Total number Fever Third trimester Clinical + CT Severe pneu- Cesarean sec- Number of
of cases: 386 (= 227/364) (= 341) scan + oro- monia (= 22) tion (= 257) death: 2
Cough Second trimes- pharyngeal Number of Vaginal deliv-
(= 165/364) ter (= 45) swab NAT death (= 2) ery (= 42),
Asymptomatic Continuing
(25/364) pregnancy
Fatigue (= 73)
(= 26/364) Spontaneous
Dyspnea abortion (= 3)
(= 21/364) Ectopic preg-
Chest tightness nancy (= 2)
Archives of Gynecology and Obstetrics (2021) 304:5–38

(21/364) Induced abor-

Headache tion (= 4)
(= 20/364)
Diarrhea
(= 17/364)
Myalgia
(= 13/364)
Sore throat
(5/364)
Malaise
(= 3/364)

NAT Nucleic Acid testing, CT computed tomography

*4 cases before delivery, 2 cases on the day of delivery, 3 cases after delivery
**Mother of twins, with typical clinical and chest CT finding of nCoV-2019 pneumonia confirmed as a nCoV-2019 after rule out of other causes although NAT was negative
***3 patients cured and discharged to continue the pregnancy, 9 patients gave birth and then cured and discharged, 1 patient with severe pneumonia intubated

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Table 2  Characteristics of neonates born from pregnant women with COVID-19 included in the systematic review
Article title Author Study type Country Number of Neonatal Neonatal clinical Neonatal Neonate test for nCoV-2019 Apgar score Neonatal
neonates maturity presentations complica- outcome

13
(= N) (= N) tions Result Diagnostic
method

Preg- Chen et al. Case study China 3 Mature infants No remarkable clini- No Negative Neonatal throat Not reported Healthy and
nant women (= 2) cal problem was compli- swab nucleic discharged
with Premature reported cations acid testing
new corona- with LBW were
virus infec- (= 1) reported
tion: clinical
characteristics
and placental
pathological
analysis of
three cases
Clinical analy- Zhu et al. Case study China 10 4 full terms, Respiratory distress Death Negative Neonatal throat 5th min Apgar Cured (= 5)
sis of 10 neo- (2 twins) 6 premature (= 6), (= 1)** swab nucleic score: In hospital
nates born to (2 SGA AND GI tract symptoms DIC acid testing 10 (= 6) (= 4)
mothers with 1 LGA) (= 4), (= 1)** 9 (= 2) Died (= 1)
2019-nCoV Fever (= 2) 8 (= 2)
pneumonia Increased heart rate
(= 1)
Vomiting (= 1)
Clinical charac- Chen et al. Case study China 9 Full-term No remarkable clini- No Negative Neonatal throat All babies with 5th None of the
teristics and babies (= 5), cal problem was compli- swab nucleic min Apgar score neonates
intrauterine birth at 36th reported cations acid testing of 9 to 10 needed
vertical week of were special
transmission gestational reported treatment
potential age (= 4*)
of COVID-
19 infection
in nine preg-
nant women:
a retrospec-
tive review
of medical
records
Analysis of Zhang Case–con- China 10 Full-term 3 neonate developed No Negative Neonatal throat Not reported None of the
the preg- et al. trol babies (= 9) bacterial pneumonia compli- swab nucleic neonates
nancy out- Premature cations acid testing needed
comes babies (= 1) were and imaging special
in preg- reported study treatment.
nant women No neona-
with COVID- tal death
19 in Hubei
Province
Archives of Gynecology and Obstetrics (2021) 304:5–38
 Table 2  (continued)
Article title Author Study type Country Number of Neonatal Neonatal clinical Neonatal Neonate test for nCoV-2019 Apgar score Neonatal
neonates maturity presentations complica- outcome
(= N) (= N) tions Result Diagnostic
method

Clinical mani- Liu et al. Case China 10 Full-term 9 neonates survived 1 neonate Negative Neonatal throat 1st min Apgar 1 dead
festations and Study babies (= 4), with no remarkable died swab nucleic score: 10 for all neonate
outcome of Premature clinical problem, due to acid testing nine alive babies because of
SARS-CoV-2 babies (= 6) 1 died due to ARDS MODS MODS
infection dur- and MODS
ing pregnancy
Lack of Verti- Li et al. Case China 1 Premature No remarkable clini- No Negative Neonatal throat Not reported Healthy and
cal transmis- Report baby in 35th cal problem was compli- swab nucleic discharged
sion of severe week of GA reported cations acid testing
acute were
respiratory reported
Archives of Gynecology and Obstetrics (2021) 304:5–38

syndrome
Coronavirus
2, China
A case of Wang et al. Case China 1 Premature No remarkable clini- No Negative Neonatal throat 5th min Apgar Healthy and
2019 Novel report baby in 30th cal problem was compli- swab nucleic score: 10 discharged
Coronavirus week of GA reported cations acid testing
in a pregnant were
woman with reported
preterm
delivery
A case report Wang et al. Case China 1 Full-term COVID-19 Pneu- No Positive Neonatal throat 5th min Apgar Healthy and
of neonatal report baby monia compli- swab nucleic score: 9 discharged
COVID-19 cations acid testing
infection in were (36th-hour
China reported birth)
Perinatal Fan et al. Case China 2 Full-term Mild neonatal pneu- No Negative Neonatal throat 5th min Apgar Healthy and
transmission report neonate monia and lympho- compli- swab nucleic score: 10 discharged
of COVID-19 (= 1) penia (= 1) cations acid testing
associated 36th week Low-grade Fever and were
SARS-CoV-2: and 5 days diffuse haziness reported
should we of GA (= 1) of lungs without
worry? patchy consolida-
tion which cured
with antibiotic

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19
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Table 2  (continued)
Article title Author Study type Country Number of Neonatal Neonatal clinical Neonatal Neonate test for nCoV-2019 Apgar score Neonatal
neonates maturity presentations complica- outcome

13
(= N) (= N) tions Result Diagnostic
method

Clinical Chen et al. Case series China 5 Full-term Fetal tachycardia No Negative Neonatal throat 5th min Apgar Healthy
analysis of neonate (= 1) compli- swab nucleic score: 10
pregnant (= 5) cations acid testing (= 5)
women with were
2019 Novel reported
Coronavirus
pneumonia
Possible Dong Case China 1 34 weeks and Elevated IgM anti- No Negative Neonatal throat 5th min Apgar Healthy and
vertical et al. report 5 days body*** compli- swab nucleic score: 10 discharged
transmission cations acid testing
of SARS- were
CoV-2 From reported
an infected
mother to her
newborn
Lung ultra- Kalafat Case Turkey 1 35 weeks and No remarkable clini- No Negative Neonatal throat 5th min Apgar Healthy
sound and et al. report 3 days cal problem was compli- swab nucleic score: 9
computed reported cations acid testing
tomographic were
findings in reported
a pregnant
woman with
COVID-19
Title: Coro- Liu et al. Case series China 3 Full-term Chorioamnionitis and No Negative Neonatal throat 5th min Apgar Survived
navirus neonates meconium aspira- compli- swab nucleic score: 9 (= 3) (= 3)
disease 2019 (= 3) tion syndrome (= 1) cations acid testing
(COVID-19) were
during preg- reported
nancy: a case
series
Maternal and Li et al. Case–con- China 17 Full-term Intrauterine fetal No Negative Neonatal throat 5th min Apgar No death
neonatal trol (= 13) distress (= 2) compli- swab nucleic score: 10 was
outcomes Premature cations acid testing (= 17) reported
of pregnant (= 4) were (= 3)****
women with LBW (= 3) reported
COVID-19
pneumonia: a
case–control
study
Archives of Gynecology and Obstetrics (2021) 304:5–38
 Table 2  (continued)
Article title Author Study type Country Number of Neonatal Neonatal clinical Neonatal Neonate test for nCoV-2019 Apgar score Neonatal
neonates maturity presentations complica- outcome
(= N) (= N) tions Result Diagnostic
method

A pregnant Zambrano Case United 1 32 weeks of No remarkable clini- No Negative Neonatal throat Not reported No death
woman with et al. report States, GA cal problem was compli- swab nucleic was
COVID-19 USA reported cations acid testing reported
in Central were
America reported
Pregnancy and Liu et al. Cross-sec- China 11 Full-term No remarkable clini- No Negative Not 5th min Apgar No death
Perinatal tional (= 8) cal problem was compli- reported***** score: 9 was
outcomes of Preterm deliv- reported cations reported
women with ery (= 3) were
Coronavi- reported
rus Disease
Archives of Gynecology and Obstetrics (2021) 304:5–38

(COVID-19)
Pneumonia:
A Preliminary
Analysis
Clinical Yu et al. Retrospec- China 7 Full-term Mild shortness of Mild pul- Negative Neonatal throat 5th min Apgar No death
features and tive (= 7) breath (= 1) monary (= 2) swab nucleic score: 9 -10 was
obstetric study infection Positive acid testing (= 7) reported
and neonatal in a neo- (= 1)******
outcomes nate with
of pregnant positive
patients with COVID-
COVID-19 19 test
in Wuhan,
China: a
retrospective,
single-center,
descriptive
study

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21
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Table 2  (continued)
Article title Author Study type Country Number of Neonatal Neonatal clinical Neonatal Neonate test for nCoV-2019 Apgar score Neonatal
neonates maturity presentations complica- outcome

13
(= N) (= N) tions Result Diagnostic
method

Neonatal Zeng et al. Cohort China 33 Full-term Fever (= 2; both with Asphyxia Negative Neonatal throat Not No death
early-onset study (= 29) positive COVID- (= 2; one (= 30) swab nucleic reported******* was
infection Preterm (= 4) 19) neonate Positive acid testing reported
with SARS Shortness of breath with (= 3)
CoV-2 in 33 (= 4; 3 with nega- negative
neonates born tive COVID-19 and COVID-
to mothers one positive) 19
With COVID- Cyanosis (= 3; 2 with infection
19 in Wuhan, negative COVID- and one
China 19 and one with neonate
positive) with
Feeding intolerance positive
(= 3; 2 with nega- COVID-
tive COVID-19 and 19 infec-
one with positive) tion)
Pneumonia
(3; all
3 with
positive
COVID-
19)
Respira-
tory dis-
tress syn-
drome
(4; 3
with
negative
COVID-
19 and
one posi-
tive)
Requiring
mechani-
cal ven-
tilation:
1 baby
with
COVID-
19 posi-
tive
Archives of Gynecology and Obstetrics (2021) 304:5–38
 Table 2  (continued)
Article title Author Study type Country Number of Neonatal Neonatal clinical Neonatal Neonate test for nCoV-2019 Apgar score Neonatal
neonates maturity presentations complica- outcome
(= N) (= N) tions Result Diagnostic
method

Mortality of Karami Case Iran 1 Stillbirth – – Not reported Not reported Apgar score:0 Fetal death
a pregnant et al. report
patient diag-
nosed with
COVID-19:
a case report
with clinical,
radiological,
and histo-
pathological
findings
Archives of Gynecology and Obstetrics (2021) 304:5–38

Unlikely Peng et al. Case China 1 Preterm Mild respiratory None Negative Neonatal throat 5th min Apgar Survived
SARS-CoV-2 report distress and anal and score: 10
vertical trans- swab and
mission from sputum and
mother to serum nucleic
child: a case acid testing
report
Severe COVID- Alzamora Case The United 1 Preterm Mild respiratory Intubation Positive Neonatal throat 5th min Apgar No death
19 during et al. report States, distress because swab nucleic score: 8 was
pregnancy USA And sporadic cough of acid testing reported
and possible mother’s (16 h after
vertical trans- sedation delivery)
mission
Preterm deliv- Zamanian Case Iran 1 Preterm Fever None Positive Neonatal throat 5th min Apgar Survived
ery in a preg- et al. report swab nucleic score: 9
nant woman acid testing
with critical
COVID-19
pneumonia
and vertical
transmission
Vaginal deliv- Xiong Case China 1 Full-term No remarkable clini- None Negative Neonatal throat 5th min Apgar Healthy and
ery report of et al. report cal problem was and anal swab score: 10 discharged
a healthy neo- reported nucleic acid
nate born to a testing
convalescent
mother with
COVID-19

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Table 2  (continued)
Article title Author Study type Country Number of Neonatal Neonatal clinical Neonatal Neonate test for nCoV-2019 Apgar score Neonatal
neonates maturity presentations complica- outcome

13
(= N) (= N) tions Result Diagnostic
method

Association of Khan et al. Case series China 17 Full-term Neonatal pneumonia No serious Negative Neonatal throat 5th min Apgar No case of
COVID-19 (= 14) (= 5) compli- (= 15) and anal swab score: 9–10 death was
infection with Preterm (= 3) 2 case of COVID-19 cations Positive nucleic acid reported
pregnancy which one of them were (= 2) testing
outcomes in developed pneu- reported
healthcare monia
workers
and general
women
Impact of Khan et al. Case China 3 Full-term No remarkable clini- None Negative Neonatal throat 5th min Apgar No case of
COVID-19 report (= 2) cal problem was (= 3) and anal swab score: 9–10 death was
infection on Preterm (= 1) reported nucleic acid reported
pregnancy testing
outcomes
and the risk
of maternal-
to- neonatal
intrapartum
transmission
of COVID-19
during natural
birth
Clinical charac- Liu et al. Retrospec- China 19 Full-term No remarkable clini- None Negative Neonatal throat 5th min Apgar No case of
teristics of 19 tive (= 17) cal problem was (= 19) and anal swab score: 9 death was
neonates born study Preterm (= 2) reported nucleic acid reported
to mothers testing
with COVID-
19
Archives of Gynecology and Obstetrics (2021) 304:5–38
 Table 2  (continued)
Article title Author Study type Country Number of Neonatal Neonatal clinical Neonatal Neonate test for nCoV-2019 Apgar score Neonatal
neonates maturity presentations complica- outcome
(= N) (= N) tions Result Diagnostic
method

COVID-19 Breslin Cohort The United 18 Full-term Respiratory distress None Negative Neonatal throat 5th min Apgar All healthy
infection et al. study States, (= 17) (= 1) (= 18; and anal swab score: 9–10 and dis-
among USA Premature One patient with includ- nucleic acid charged
asymptomatic (= 1) congenital disease ing one testing
and sympto- intermedi-
matic preg- ate result
nant women: which
Two weeks considers
of confirmed as negative
presentations because of
to an affiliated low detec-
Archives of Gynecology and Obstetrics (2021) 304:5–38

pair of New tion)

York City
hospitals
Clinical Yang et al. Case–con- China 20******** Mean ± SD Fever (= 1 from None Negative Neonatal throat Not reported No case of
features and trol GA: COVID-19 positive and anal swab death was
outcomes 38.2 ± 2.3 mother) nucleic acid reported
of pregnant testing
women
suspected of
Coronavirus
Disease 2019
Asymptomatic Renbin Case China 1 Full-term No remarkable clini- None Negative Neonatal throat Not reported Healthy and
COVID-19 et al. report cal problem was swab nucleic discharged
in a pregnant reported acid testing
woman with
typical chest
CT manifesta-
tion: a case
report
Chest CT Liao et al. Case China 1 Preterm No remarkable clini- None Negative Neonatal throat Not reported No case of
findings in report cal problem was and anal swab death was
a pregnant reported nucleic acid reported
patient with testing
2019 Novel
Coronavirus
Disease

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25
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Table 2  (continued)
Article title Author Study type Country Number of Neonatal Neonatal clinical Neonatal Neonate test for nCoV-2019 Apgar score Neonatal
neonates maturity presentations complica- outcome

13
(= N) (= N) tions Result Diagnostic
method

Infants born Chen et al. Case China 4 Full-term No remarkable clini- None Negative Neonatal throat Not reported No case of
to mothers report (= 4) cal problem was (= 4) and anal swab death was
with a new reported nucleic acid reported
Coronavirus testing
(COVID-19)
Anesthetic Song et al. Case China 1 Preterm No remarkable clini- None Negative Neonatal throat 5th min Apgar Healthy and
management report cal problem was swab nucleic score: 9 discharged
for emergent reported acid testing
cesarean
delivery in
a parturient
with recent
diagnosis of
Coronavirus
Disease 2019
(COVID-19):
a case report
Clinical charac- Yang et al. Case series China 7 Full-term Mild respiratory None Negative Neonatal throat 5th min Apgar No case of
teristics and (= 3) distress syndrome (performed swab nucleic score: 9–10 death was
risk assess- Preterm (= 4) (= 2) for 6 neo- acid testing reported
ment of new- Vomiting and hypo- nates)
borns born to glycemia (= 1)
mothers with
COVID-19
COVID-19 in Breslin Case series The United 2 Full-term No remarkable clini- None Negative Neonatal throat Not reported No case of
pregnancy: et al. States, (= 2) cal problem was (performed swab nucleic death was
early lessons USA reported for one acid testing reported
neonate)
Antibodies in Zeng et al. Case study China 6 Not reported No remarkable clini- None Negative Neonatal throat Not reported No case of
Infants Born cal problem was (= 6) and serum death was
to mothers reported********* swab nucleic reported
with COVID- acid testing
19 Pneumonia
Novel Corona- Zhang Case series China 2 Full-term Shortness of breath None Positive Neonatal throat Not reported No case of
virus infection et al. (= 2) (= 1) swab nucleic death was
in newborn acid testing reported
babies under
28 days in
China
Archives of Gynecology and Obstetrics (2021) 304:5–38
 Table 2  (continued)
Article title Author Study type Country Number of Neonatal Neonatal clinical Neonatal Neonate test for nCoV-2019 Apgar score Neonatal
neonates maturity presentations complica- outcome
(= N) (= N) tions Result Diagnostic
method

Clinical char- Chen et al. Retrospec- China 70 Full-term No remarkable clini- None Negativeϕ Neonatal throat 5th min Apgar No case of
acteristics tive (2 set of (= 56) cal problem was swab nucleic score: 8-9ϕ death was
of pregnant study twins) Preterm (14) reported acid testing reported
women with
Covid-19 in
Wuhan, China
Total results Total Full-term DIC (= 2) Negatives Survived
number of (= 210/276) MODS (= 208) (= 299)
neonates: Premature (= 1) And positive died (= 3)
302 (= 65/276) (= 11)
stillbirth (= 1)
Archives of Gynecology and Obstetrics (2021) 304:5–38

MODS Multiple organ dysfunction syndrome, ARDS Acute respiratory distress syndrome, DIC Disseminated intravascular coagulation, GA gestational age, SGA Small for gestational age, LGA
Large for gestational age, LBW low birth weight, C-Section Cesarean section
We considered GA < 37 weeks as preterm delivery
*One complicated with pre-eclampsia, one with history of 2 stillbirth, one with history of 2 previous c-sections and irregular contractures, and one with premature rupture of membranes
**One neonate in which first symptom was increased heart rate developed refractory shock and gastric bleeding which lead to death, another neonate with shortness of breath and moaning and
later with DIC that cured
***SARS-CoV-2 IgG level: 140.32 AU/mL and IgM level: 45.83 AU/mL 2 h after birth and also 16 days after birth repeated test revealed IgG level of 69.94 AU/mL and IgM level of 11.75 AU/
mL
****The specimens collected from three neonates whom delivered by cesarean section
*****The study claimed that no COVID-19 infection was represented in neonates but did not clarified by which method -clinical or nucleic acid testing-
******Specimens collected from three neonates and positive sample was collected 36 h after birth
*******Except one of infected neonates with confirmed COVID-19 infection born with need of resuscitation and Apgar score of 3, 4, 5 in 1, 5 and 10 min
********The total number of neonates were 57 and 20 neonates tested for COVID-19 but study did not clarify how many neonates belong to the case group
*********2 neonates had elevated serum IgM levels
ϕNasopharyngeal swab was taken from 8 neonates
ϕϕApgar score was measured for 66 neonates

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27
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Table 3  A summary of studies on pregnancy outcomes in pregnant women with COVID-19 included in the systematic review
Article title Author Study type Country Placental test for nCoV-2019 Pregnancy complications Further information
nucleic acid

13
Result Method

Pregnant women with Chen et al. Case study China Negative RT-PCR Not reported Umbilical cord and fetal mem-
new coronavirus infection: branes were tested
clinical characteristics and and went negative
placental pathological analy-
sis of three cases
Clinical analysis of 10 neo- Zhu et al. Case study China Not reported Not reported Premature rupture of mem- No further samples were
nates born to mothers with branes (= 3), examined
2019-nCoV pneumonia One polyhydramnios,
One oligohydramnios
Clinical characteristics and Chen et al. Case study China Not reported Not reported Premature rupture of Mem- All amniotic fluid, cord blood,
intrauterine vertical trans- branes (= 2), breastmilk samples from six
mission potential of COVID- Fetal distress (= 2) patients were negative (3
19 infection in nine preg- cases has unsuccessful sample
nant women: a retrospective collection)
review of medical records
Analysis of the pregnancy out- Zhang et al. Case–control China Not reported Not reported Pre-eclampsia (= 1), No further samples were
comes in pregnant women PROM (= 3), examined
with COVID-19 in Hubei Fetal distress (= 1),
Province Premature birth (= 3),
Asphyxia (= 1)
Clinical manifestations and Liu et al. Case study China Not reported Not reported Fetal distress (= 3), No further samples were
outcome of SARS-CoV-2 PROM (= 1), examined
infection during pregnancy Stillbirth (= 1)
Lack of vertical transmission Li et al. Case report China Negative RT-PCR Not reported Serum, urine, feces, amniotic
of severe acute respiratory fluid, umbilical cord blood
syndrome Coronavirus 2, and placenta, and breast milk
China samples were negative
A case of 2019 Novel Corona- Wang et al. Case report China Negative RT-PCR Not reported Amniotic fluid and cord blood
virus in a pregnant woman were negative
with preterm delivery
A case report of neonatal Wang et al. Case report China Negative RT-PCR Not reported Cord blood and mother’s breast
COVID-19 infection in milk were negative
China
Perinatal transmission of Fan et al. Case report China Negative RT-PCR Not reported Umbilical cord blood, amniotic
COVID-19 associated fluid, vaginal swabs, and
SARS-CoV-2: should we mother’s breast milk were
worry? negative
Clinical analysis of pregnant Chen et al. Case series China Not reported Not reported Pre-eclampsia (= 1) Not reported
women with 2019 novel Gestational diabetes (= 2)
coronavirus pneumonia
Archives of Gynecology and Obstetrics (2021) 304:5–38
 Table 3  (continued)
Article title Author Study type Country Placental test for nCoV-2019 Pregnancy complications Further information
nucleic acid
Result Method

Possible vertical transmis- Dong et al. Case report China Not reported Not reported Not reported Mother’s vaginal discharge and
sion of SARS-CoV-2 from breastmilk were negative for
an infected mother to her COVID-19 PCR test result
newborn
Lung ultrasound and com- Kalafat et al. Case report Turkey Negative RT-PCR Not reported Breast milk and cord blood
puted tomographic findings were negative
in a pregnant woman with
COVID-19
Coronavirus disease 2019 Liu et al. Case series China Negative RT-PCR Gestational hypertension Breast milk, cord blood, amni-
(COVID-19) during preg- otic fluid, neonatal serum, and
nancy: a case series mothers’ vaginal mucosa were
Archives of Gynecology and Obstetrics (2021) 304:5–38

negative
Maternal and neonatal out- Li et al. Case–control China Not reported Not reported gestational diabetes mellitus Not reported
comes of pregnant women (= 3)
with COVID-19 pneumonia: PROM (= 1)
a case–control study gestational hypertension (= 3),
hypothyroidism (= 2), pre-
eclampsia (= 1)
Sinus tachycardia (= 1)
Fetal distress (= 2)
A pregnant woman with Zambrano et al. Case report United States, Not reported Not reported gestational hypertension Neonate’s blood sample was
COVID-19 in Central USA and hypothyroidism negative
America
Pregnancy and perinatal out- Liu et al. Cross-sectional China Not reported Not reported Placenta previa (= 1) Not reported
comes of women with Coro-
navirus Disease (COVID-19)
pneumonia: a preliminary
analysis
Clinical features and obstetric Yu et al. Retrospective study China Not reported Not reported Uterine scarring (= 3) Not reported
and neonatal outcomes Hypothyroidism (= 1)
of pregnant patients with
COVID-19 in Wuhan,
China: a retrospective,
single-center, descriptive
study
Neonatal Early-Onset Infec- Zeng et al. Cohort study China Not reported Not reported PROM (= 3) Not reported
tion with SARS CoV-2 in 33
Neonates Born to Mothers
With COVID-19
in Wuhan, China

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29
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Table 3  (continued)
Article title Author Study type Country Placental test for nCoV-2019 Pregnancy complications Further information
nucleic acid

13
Result Method

Mortality of a pregnant patient Karami et al. Case report Iran Not reported Not reported Not reported Not reported
diagnosed with COVID-19:
A case report with clinical,
radiological, and histopatho-
logical findings
Unlikely SARS-CoV-2 vertical Peng et al. Case report China Negative RT-PCR Not reported Amniotic fluid, vaginal mucosa,
transmission from mother to cord blood, and breast milk
child: a case report were all negative
Severe COVID-19 during Alzamora et al. Case report The United States, Not reported Not reported Diabetes mellitus Not reported
pregnancy and possible USA
vertical transmission
Preterm delivery in a preg- Zamanian et al. Case report Iran Not reported Not reported Not reported Cord blood was negative, but
nant woman with critical Amniotic fluid was positive
COVID-19 pneumonia and
vertical transmission
Vaginal delivery report of a Xiong et al. Case report China Negative RT-PCR Not reported Amniotic fluid was negative
healthy neonate born to a
convalescent mother with
COVID-19
Association of COVID-19 Khan et al. Case series China Not reported Not reported 5 women with other complica- Not reported
infection with pregnancy tions
outcomes in healthcare
workers and general women
Impact of COVID-19 infection Khan et al. Case report China Not reported Not reported Not reported The cord blood sample was
on pregnancy outcomes and negative
the risk of maternal-to- neo-
natal intrapartum transmis-
sion of COVID-19 during
natural birth
Clinical characteristics of 19 Liu et al. Retrospective study China Not reported Not reported Not reported Breast milk sample, amniotic
neonates born to mothers fluid, and cord blood were
with COVID-19 negative
COVID-19 infection among Breslin et al. Cohort study The United States, Not reported Not reported PROM Not reported
asymptomatic and sympto- USA
matic pregnant women: two
weeks of confirmed presen-
tations to an affiliated pair of
New York City hospitals
Archives of Gynecology and Obstetrics (2021) 304:5–38
 Table 3  (continued)
Article title Author Study type Country Placental test for nCoV-2019 Pregnancy complications Further information
nucleic acid
Result Method

Clinical features and out- Yang et al. Case–control China Not reported Not reported Not reported Not reported
comes of pregnant women
suspected of Coronavirus
Disease 2019
Asymptomatic COVID-19 in a Renbin et al. Case report China Not reported Not reported Not reported Not reported
pregnant woman with typical
chest CT manifestation: a
case report
Chest CT findings in a preg- Liao et al. Case report China Negative RT-PCR Not reported Amniotic fluid and cord blood
nant patient with 2019 Novel were negative
Coronavirus Disease
Archives of Gynecology and Obstetrics (2021) 304:5–38

Infants born to mothers with a Chen et al. Case report China Not reported Not reported Placenta (= 1) Not reported
new Coronavirus (COVID-
19)
Anesthetic management for Song et al. Case report China Not reported Not reported Not reported Not reported
emergent cesarean delivery
in a parturient with recent
diagnosis of Coronavirus
Disease 2019 (COVID-19):
a case report
Clinical characteristics and Yang et al. Case series China Not reported Not reported Not reported Cord blood and amniotic fluid
risk assessment of new- were negative
borns born to mothers with
COVID-19
COVID-19 in pregnancy: early Breslin et al. Case series The United States, Not reported Not reported Type 2 diabetes mellitus (= 2) Not reported
lessons USA
Antibodies in infants born to Zeng et al. Case study China Not reported Not reported Not reported Not reported
mothers with COVID-19
pneumonia
Novel Coronavirus infection Zhang et al. Case series China Not reported Not reported Not reported Not reported
in newborn babies under 28
Days in China
Clinical characteristics of Chen et al. Retrospective study China Not reported Not reported Not reported Breast milk of three mothers
pregnant women with were negative for the virus
Covid-19 in Wuhan, China
Total results All samples RT-PCR
examined were
negative

RT-PCR Reverse transcription-polymerase chain reaction, PROM Premature rupture of membranes

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31
32 Archives of Gynecology and Obstetrics (2021) 304:5–38

included myalgia, diarrhea, dyspnea, headache, and chest all negative for SARS-CoV-2 RNA detection. The fourth
tightness. There were two women with specific presenta- one suffered from pneumonia and needed intubation at
tions: one with Cholecystitis [50] and another with oil intol- birth. Sixteen hours after birth, the neonate tested positive
erance [67]. for SARS-CoV-2 RNA with throat swab nucleic acid test-
For nearly all pregnant women, the diagnosis was made ing [74]. This neonate was later extubated and discharged
based on a combination of clinical symptoms, nucleic acid without any complications. The fifth one was a premature
testing for the novel coronavirus, and computed tomography baby with the gestational age of 31 weeks and 2 days. This
(CT). As for the general population, some pregnant patients neonate had an Apgar score of 3, 4, and 4 at the first, fifth,
(n = 44) had a negative SARS-CoV-2 test but displayed clini- and tenth minute after delivery and required resuscitation
cal manifestations and abnormalities in CT scan related to [66]. This neonate was later confirmed as a definite case of
COVID-19 [50, 53, 55]. COVID-19 and developed DIC. Vital signs were success-
Twenty-two (6.0%) pregnant patients developed severe fully stabilized on the day of 14. This neonate had close
pneumonia. Among them, 10 cases (2.8%) required mechan- contact with the mother after delivery.
ical ventilation and therefore were admitted to the intensive Except for the babies mentioned above, most babies born
care unit (ICU) [42, 44, 53, 58, 60, 63, 65, 73, 74]. Two of alive had a 5-min Apgar score of 8 and 9 (Table 2). A total
these ten patients died from severe pneumonia and multiple of 219 neonates underwent nasopharyngeal specimen col-
organ dysfunction [65, 73]. lection for SARS-CoV-2 nucleic acid testing. Of them, 11
The vast majority of patients were in their third trimester tested positive, and two of which were described above.
of pregnancy, and only 45 cases were in the first or second A study by Wang S et al. reported a neonate with a posi-
trimester (12.4%). Of the total number of 299 births, there tive throat specimen for COVID-19 [48]. This neonate had
were 257 (86%) cesarean sections, and 42 (14%) vaginally early close contact with COVID-19 positive mother, and the
completed. Zhang L et al. and Breslin et al. reported obstet- specimen was collected 36 h after birth, while the placental
ric reasons such as premature rupture of membrane, fetal and cord blood specimens taken at birth were negative. Yu
distress, and other indications for the Cesarean section [44, N et al. collected nasopharyngeal swab from three neonates,
60]. Chen et al. reported that 38 of 63 cases who under- of which one was positive for COVID-19 [56]. This speci-
went cesarean sections claimed to have a fear of COVID- men was collected 36 h after birth, and that no nucleic acid
19 [53]. There were three cases of spontaneous abortions, testing was performed for the placenta, cord blood, or other
two ectopic pregnancy, and four induced abortions. Preg- pregnancy products.
nant women seeking induced abortion were most afraid of In a cohort study of 33 neonates, there were two neonates
COVID-19 and its potential effects on pregnancy outcomes with a positive test [66]. Both neonates survived. None of
[53]. the placenta, cord blood, and other pregnancy products were
tested for COVID-19 in this study. Zamanian et al. reported
Neonatal outcomes another newborn with a positive test who had fever with-
out any further complications. By the end of the study, the
Thirty-seven studies included a total of 302 neonates from neonate was healthy and stable [73]. Also, the other four
mothers with COVID-19. Two studies have not indicated the COVID-19 positive neonates did not develop any complica-
timing of birth [43, 57]. Of the studies that provided data, tions and survived [46]. Seventeen studies reported the col-
there were 210 full-term and 65 preterm neonates. lection of the amniotic fluid, cord blood, placenta, and breast
Karami et al. reported the death of a mother from milk samples, and all tested negative except one amniotic
COVID-19 and also her fetus [65]. The dead baby was born fluid sample. Zamanyan et al. reported a pregnant woman
with an Apgar score of 0, did not respond to resuscitation, with COVID-19 infection and her positive newborn. Nucleic
and was not considered for COVID-19 diagnostic tests. Of acid testing was done on the cord blood and amniotic fluid
the babies born alive from mothers with COVID-19, five samples [73]. Whereas no viral RNA was detected in the
newborns faced critical conditions. One of them presented cord blood, the amniotic fluid was positive for viral RNA.
with a fast heart rate developed gastric bleeding and refrac-
tory shock later and died. The second complicated case was
a premature newborn born from a mother, who had a diag- Pregnancy outcomes
nosis of severe COVID-19 pneumonia [50]. This neonate
showed shortness of breath at presentation and developed In a case–control study by Zhang et al., there was no differ-
disseminated intravascular coagulation (DIC). This case ence between 16 pregnant women with COVID-19 and 45
could be cured. The third neonate died due to the multiple pregnant women without COVID-19 in terms of pregnancy
organ dysfunction syndrome and could not survive [58]. complications, including eclampsia, fetal distress, and pre-
The nasopharyngeal samples of these three babies were mature rupture of membrane (Table 3) [44].

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Archives of Gynecology and Obstetrics (2021) 304:5–38 33

Discussion website established to gather comprehensive data on moth-

ers with COVID-19 who give birth around this country
This systematic review included 386 pregnant women reports cesarean rate as about 37.5% by the last of January
with COVID-19. There were 257 cesarean sections and 2021 [79]. These national reports come from two highly
42 vaginal delivery. This relatively higher rate of cesar- developed countries equipped with the best available strat-
ean sections would reflect the existence of indications for egies to control the COVID-19 and related stress. It may
a cesarean section as well as the role of fear of vertical positively impact pregnant women’s psychological status
transmission. Most women represented common symp- when choosing delivery method. Another possible reason
toms, and two deaths occurred (death rate of 0.5%). While for the difference in results is the method of data gather-
COVID-19 has, to date, caused a total number of 163,097 ing. This study is a systematic review including studies
deaths out of 2.4 million confirmed cases, corresponding pertinent to different countries. At the time of systematic
to the mortality rate of about 7% [77]. Therefore, com- search by the last of April 2020, many studies reporting
pared to the general population, pregnant women have not pregnant women with COVID-19 were case reports, case
shown a more aggressive form of COVID-19. series, or studies with a low sample size. Still, the two
Among the total number of 302 neonates from mothers mentioned studied were at a grander scale, which may
with COVID-19, there were nasopharyngeal specimens effectuate the result. On the other hand, in our study, there
collected from 219 neonates, of which 11 tested positives is no patient from England or Germany, and most of the
for SARS-CoV-2. One study reported a positive SARS- patients are from China. Although the CRONOS register is
CoV-2 for amniotic fluid samples [73]. Interestingly, two a large-scale registry, it lacks clinically important details,
studies reported high IgM levels in neonates who tested such as signs, symptoms, and history, about every indi-
negative for SARS-CoV2 [43, 69]. Because there is no vidual registered in this program.
possibility of IgM transfer through the placenta, this labo- Since December 2019, COVID-19 has been a resident
ratory data can be suggestive of vertical transmission of of the world. Early efforts ranged from the development of
COVID-19. More studies are required to investigate the diagnostic assays [80–83] and specific therapeutics [84–102]
potential of COVID-19 to be transmitted via the vaginal to optimizing health monitoring [103, 104]. Despite this
route and the possible association between maternal infec- effort, in addition to our knowledge and experience from
tion with COVID-19 and long-term child health. the recent outbreaks [105], it mainly relied on non-pharma-
Nearly all mothers were healthy women without under- cological interventions to control the pandemic, e.g., quaran-
lying severe diseases such as diabetes mellitus, cardiovas- tine and social isolation [106, 107]. Such a condition triggers
cular disease, and autoimmune diseases. Therefore, further stress [108]. The stress was, in particular, of high level at the
research is necessary to evaluate whether or not ethnicity/ time when the outbreak was initiated. Growing knowledge
race, maternal comorbidities, and pregnancy stage would about different aspects of the disease, namely about the ori-
influence the course of COVID-19 in pregnancy and how gin and pathogenesis of disease varying dependent on the
this, in turn, would affect delivery complications. immunogenetic background and the presence of comorbidi-
Finally, one crucial issue which remained unresolved ties [4, 109–120], could protect against the stress and related
is the psychosocial effects of the COVID-19 outbreak on damage, which is potentially critical in pregnant women and
mental health during pregnancy. Pregnant women fre- their neonates. Our review included studies conducted in
quently report psychosocial stress, depression, and panic the first six months of the pandemic when there was a high
disorder. In particular, there is a direct correlation between degree of stress and fear. This explains why the cesarean
the level of antenatal psychosocial stress and the risk of rate we calculated is relatively high, and also one can simply
poor pregnancy outcomes in the manner that the higher predict its reduction over time.
the antenatal psychosocial stress, the greater the risk of A major limitation is the lack of data in developing coun-
poor pregnancy outcomes. Therefore, pregnancy might tries. Perinatal care is a crucial issue in less developed coun-
be complicated during the COVID-19 outbreak, even if tries, while pregnant women in these countries may not have
women do not get infected by the virus. feasible access to health care facilities. Besides, insufficient
In this study, from 386 parturient women with COVID- perinatal care leads to a high rate of perinatal adverse events
19, 257 out of 299 patients gave birth by cesarean sec- [122] while worsening during the pandemic. It is, therefore,
tion, which means the cesarean section rate among these important to gather enough data on pregnant women and
patients was about to 86%, which is very high. In a national their neonates in these countries. However, when this study
cohort study reported by Knight et al., the cesarean rate in was carried out, the data on less developed countries were
pregnant women with COVID-19 in the United Kingdom too scarce, which may be because of lack of diagnostic facil-
was about 59% [78]. In Germany, the CRONOS register ities in these countries, insufficient referring, or reporting
system. So further investigations are necessary to discover

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34 Archives of Gynecology and Obstetrics (2021) 304:5–38

the impact of COVID-19 on perinatal events in developing 6. Nejadghaderi SA, Heidari A, Shakerian N, Saghazadeh A,
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The present systematic review suggests that clinical features 8. Vakhshoori M, Heidarpour M, Shafie D, Taheri M, Rezaei
N, Sarrafzadegan N (2020) Acute cardiac injury in COVID-
and prognosis of pregnant women with COVID-19 may 19: a systematic review and meta-analysis. Arch Iran Med
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previous studies [121]. Still, this result should not lead to 9. Yazdanpanah N, Saghazadeh A, Rezaei N (2020) Anosmia: a
pregnant women ignore their suspect signs and symptoms missing link in the neuroimmunology of coronavirus disease
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to present themselves to medical care centers. It is crucial to org/​10.​1515/​revne​uro-​2020-​0039
provide optimum health care for pregnant women during the 10. Heidarpour M, Vakhshoori M, Abbasi S, Shafie D, Rezaei N
COVID-19 pandemic and follow their health status, espe- (2020) Adrenal insufficiency in coronavirus disease 2019: a
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COVID-19 in pregnant women are not different from those M, Rezaei N (2020) Cutaneous lesions and COVID-19: cystic
of the disease reported in society. Despite the high rate of painful lesion in a case with positive SARS-CoV-2. Dermatol
contagion of COVID-19, vertical transmission of the novel Ther 33(6):e14266. https://​doi.​org/​10.​1111/​dth.​14266
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79. https://​doi.​org/​10.​1016/j.​pedn.​2020.​10.​020
Author contributions MM: Conceptualized the study, conducted data- 14. Lotfi M, Hamblin MR, Rezaei N (2020) COVID-19: transmis-
base search, search results screening, detailed review, and prepared sion, prevention, and potential therapeutic opportunities. Clin
the initial draft. AS: Prepared the final draft. NR: Supervised the pro- Chim Acta 508:254–266. https://​doi.​org/​10.​1016/j.​cca.​2020.​05.​
ject and critically appraised the manuscript. All authors have read and 044
approved the manuscript. 15. Lotfi M, Rezaei N (2020) SARS-CoV-2: a comprehensive review
from pathogenicity of the virus to clinical consequences. J Med
Declarations Virol 92(10):1864–1874. https://​doi.​org/​10.​1002/​jmv.​26123
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Conflict of interest The authors declare that they have co conflicts of
https://​doi.​org/​10.​1080/​21645​515.​2020.​17996​69
interest.
17. Yazdanpanah F, Hamblin MR, Rezaei N (2020) The immune sys-
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